The proposed research entails immunochemical studies of pemphigus antigen, serologic and immunopathologic studies of pemphigus antibody reactions and investigations on the possible etiology of pemphigus antibodies. Specifically, the antigen in skin and mucous membranes which reacts with pemphigus antibodies would first be isolated, purified, characterized biochemically and analysed for molecular weight and shape. With purified preparations of pemphigus antigen, other more sensitive methods for detecting pemphigus antibodies would be elaborated. Also animal immunization programs would be initiated with a view toward elaborating an experimental model system of pemphigus using purified pemphigus antigen preparation for immunization. Detailed studies of mechanisms by which pemphigus antibodies contribute to the production of tissue damage would be carried out. They would include studies on the passive transfer of pemphigus, investigations on the participation of complement and studies on possible factors responsible for inciting the formation of pemphigus antibodies would be undertaken. Specifically, exploratory studies of the etiology of pemphigus antibodies would be based on three working hypotheses, namely a viral etiology, drug induction and genetic factors. In view of the fact that the immunofluorescent methods for detecting pemphigus antibodies afford useful and reliable tests for the diagnosis of pemphigus and for the control of dosages of cortico-steriods, these test methods can affect savings in the hospitalization costs of this country that are estimated to be at least five times greater than the support requested for this project. It is anticipated that the proposed research will result in even greater savings in hospitalization costs.